Nonplanar Tub-shaped Benzocyclooctatetraenes via Halogen-Radical Ring Opening of Dihydrobiphenylenes

Nonplana Tub-Shaped Benzocyclooc a e aenes ia Halogen-
Radical Ring Opening o Dihyd obiphenylenes
Jesus Bello-Ga cía, Damián Padín, Jesus A. Va ela, and Ca los Saá*
Ci e This: O g. Le . 2021, 23, 5539−5544
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sıSuppo ing In o ma ion
ABSTRACT: A no el andem Ru-ca alyzed [2+2+2] cyclo-
addi ion o a ylenynes o dihyd obiphenylenes ollowed by
halogen- adical ing opening has been de eloped o he
cons uc ion o ub-shaped halogena ed benzocyclooc a e aenes
(bCOT’s). C oss-couplings and Diels−Alde eac ions o he
b omina ed bCOT’s allow he o ma ion o he co esponding
eigh -membe ed ing- used PAH’s. The halogen- adical ing opening p obably occu s ia a selec i e o ma ion o a bis-allyl adical a
he 1,3-cyclohexadiene moie y, halogena ion a he b idgehead ca bon, and finally elec ocyclic ing opening.
Cyclooc a e aenes (COT) a e nonplana ub-shaped
hyd oca bon compounds ha ing a D2dcon o ma ion
(mo e s able in i s dynamic equilib ium han he plana D4h
and delocalized D8hcon o ma ions) ha ha e a ac ed a g ea
deal o in e es due o hei elec onic p ope ies ha esul
om ha ing cyclic conjuga ed eigh -π-elec on sys ems.
1
They
a e also e y use ul s e ically demanding ligands o me als.
2
These impo an ea u es igge ed an eno mous effo
h oughou he yea s ha aimed o de elop and efficien
syn hesis o hese a che ypical medium-sized ca bocycles
3
wi h
he aim o unde s anding hei a oma ic and an ia oma ic
p ope ies acco ding o Huckel’s ules.
4
Mo e ecen ly,
nanog aphenes con aining nonhexagonal ings a e being
conside ed as ideal models o de ec i e g aphene o building
new semiconduc o ma e ials.
5
In pa icula , dis o ion om
plana i y caused by he p esence o eigh -membe ed ings o
he in oduc ion o [8]ci culene moie ies ha induce a deep
cu a u e in he a oma ic la ice and deeply influence he
elec onic and op ical p ope ies has a ac ed conside able
a en ion.
6
Consequen ly, he de elopmen o efficien
syn he ic me hods o COT-embedded a enes is g ea ly
significan and in high demand. In his con ex , syn he ic
app oaches o dbCOT’s,
7
dbCOTP’s,
8
ibCOT’s,
9
and
e aphenylenes
10
a e ela i ely well s udied while he simple
benzocyclooc a e aenes (bCOT’s) ha e ecei ed significan ly
less syn he ic a en ion (Scheme 1).
11
The pa en benzocy-
clooc a e aene uni had also been obse ed in pionee
Gun he ’s
12
s udies o Bi ch educ ion o biphenylene in
which he double p o ona ion o he dianion occu ed a he
b idgehead posi ion gi ing 4a,8b-dihyd obiphenylene.
13
This
eac i e species e y apidly e ol ed o he mo e s able
benzocyclooc a e aene ia he mal elec ocyclic ing opening
(Scheme 1).
On he con a y, a mild and powe ul me hod o assembling
1,3-cyclohexadiene uni s (dihyd obiphenylene isome s) had
been ecen ly de eloped in ou g oup ia Ru(II)-ca alyzed
[2+2+2] cycloaddi ion o a ylenynes and alkynes.
14
This ype
o cyclohexadiene has been u ilized in efficien syn he ic
manipula ions such as oxida ions and Diels−Alde eac ions.
15
Mo eo e , a andem Ru-ca alyzed [2+2+2] cycliza ion/iodine-
media ed ing expansion o enediynes led o a s aigh o wa d
Recei ed: June 7, 2021
Published: July 6, 2021
Scheme 1. COT-Embedded Polycyclic A enes, Bi ch
Reduc ion o Biphenylene, and Fo ma ion o
Cyclooc a e aenes by Halogen-Radical Ring Opening o
1,8b-Dihyd obiphenylenes
Le e pubs.acs.o g/O gLe
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assembly o benzo- used b idged ke ones.
16
Howe e , o he
bes ou knowledge, he adical opening o benzo- used
cyclohexadienes has no been in es iga ed e en hough such
combined p ocesses ha e syn he ic po en ial o accessing
in e es ing unc ionalized scaffolds. He ein, we epo an
efficien andem p ocess based on a Ru-ca alyzed [2+2+2]
cycloaddi ion o a ylenynes 1wi h alkynes 2 o 1,8b-
dihyd obiphenylenes 3
14
ollowed by halogen- adical ing
opening o benzocyclooc a e aenes 4(Scheme 1). The
halogena ed (mainly, b omo de i a i es) bCOT’s ha e p o ed
o be p i ileged unc ionalized s uc u al uni s o accessing
PAH’s ha combine a oma ic and an ia oma ic p ope ies.
17
Inspi ed by Gun he ’s obse a ions, we began ou
in es iga ion by examining he well-known Wohl−Ziegle
b omina ion
18
o dihyd obiphenylene 3a. Thus, as a p oo o
concep , he use o NBS and AIBN as adical ini ia o s in CCl4
a p omo ed he o ma ion o he desi ed b omobenzocy-
clooc a e aene 4a, al hough in low yield (Table 1, en y 1).
G a i yingly, when he eac ion empe a u e is inc eased a
eflux, he yield o 4a inc eases o 89% (Table 1, en y 2).
O he sol en s we e hen es ed. The use o chlo ina ed
sol en s like CHCl3o CH2Cl2o nonpola hep ane o pola
CH3CN affo ded 4a bu in lowe yields (Table 1, en ies 3−6).
By con as , pola e he eal o ap o ic sol en s such as 1,4-
dioxane o DCE and a nonpola sol en like benzene ga e 4a
in ai ly good yields (Table 1, en ies 7−9). Expe imen al
eac ion condi ions using CCl4as a sol en we e hen
examined. Thus, pe o ming he eac ion in he absence o
ligh led o a lowe yield o 4a (Table 1, en y 10) as did no
using AIBN as a adical ini ia o (Table 1, en y 11). In
addi ion, he p esence o NBS is manda o y o he
consump ion o s a ing p oduc 3a, while he es ga e ise
o a complex mix u e (Table 1, en y 12).
19
The use o o he
halogen sou ces (NIS and NCS) is also easible, affo ding he
co esponding iodina ed (4a′) and chlo ina ed (4a″)
benzocyclooc a e aenes albei in lowe yields (Table 1, en ies
13 and 14).
Wi h he op imized condi ions in hand, we nex in es iga ed
he scope o he eac ion (Scheme 2). Fo dihyd obipheny-
lenes 3a ising om elec on- ich a ylalkynes 2and a ylenyne
1a (R1= H), ei he he ialkoxyphenyl 3b, he6-
me hoxynaph hyl 3c, o he he e oa yl 3- hiophene 3d beha es
simila ly gi ing ai ly good yields o he co esponding bCOT’s
4b−d. No unexpec edly, he pa en phenyl dihyd obipheny-
lene 3e affo ds he benzocyclooc a e aene 4e in a mode a e
yield (48%), p obably due o he lowe elec on ichness o he
influen ial a yl ing in ol ed in he elec ocyclic opening.
20
Cu iously, wi h an ex ended conjuga ed π-sys em, such as in
dihyd obiphenylene 3 , he ing opening was a o ably affec ed
gi ing ise o he biphenyl benzocyclooc a e aene 4 in a ai ly
good yield. On he con a y, dihyd obiphenylenes 3a ising
om he elec on- ich dialkoxy a ylenyne 1b (R1/R1=
OCH2O) and elec on- ich alkynes 2ga e ise o he
co esponding benzocyclooc a e aenes 4g−iin mode a e o
good yields, showing he e sa ili y o combining one o wo
elec on- ich pa ne s. In e es ingly, he inyl subs i uen on
dihyd obiphenylene 3j, de i ed om Ru-ca alyzed dime iza-
ion o 1-e hynyl-4-me hoxy-2- inylbenzene 1c,
14
o he
e hynyl subs i uen on 3k [ om Ru-ca alyzed cycloaddi ion
o 1d (R1= alkynyl) and 2a] emained in ac unde he adical
condi ions gi ing he co esponding s y enic bCOT 4j and
ace ylenic bCOT 4k in ai ly good yields ha migh be capable
o u u e manipula ions.
21
Table 1. Op imiza ion o Halogen-Radical Ring Opening o
1,8b-Dihyd obiphenylene 3a o
Halobenzocyclooc a e aenes 4a (X = B ), 4a′(X = I), and
4a″(X = Cl)
a
en y sol en T(°C) yield o 4a
b
1 CCl4 30
2 CCl4 eflux 85
3 DCM eflux 32
4 CHCl3 eflux 38
5 hep ane eflux 44
6CH
3CN eflux 40
7 1,4-dioxane eflux 61
8 DCE eflux 66
9 benzene eflux 65
10 CCl4(da kness) eflux 53
11 CCl4(no AIBN) eflux 30
12 CCl4(no NBS) eflux SM (50)
13
c
CCl4 eflux 77, 4a′
14
d
CCl4 eflux 36, 4a″
a
Reac ion condi ions: 3a (0.2−0.3 mmol) in sol en (0.036 M), NBS
(1.1 equi ), AIBN (0.11 equi ), 1−1.5 h.
b
Isola ed yield.
c
NIS.
d
NCS.
Scheme 2. Radical Ring Opening o Dihyd obiphenylenes 3
o bCOT’s4
a
a
Reac ion condi ions: 3 (0.2−0.3 mmol) in CCl4(0.036 M), NBS
(1.1 equi ), AIBN (0.11 equi ), 1−1.5 h. Isola ed yield. The ORTEP
d awing o 4a shows ellipsoids a he 50% con ou p obabili y le el.
b
The eac ion ime was 4 h.
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In e es ingly, he he e oannula ed benzocyclooc a e aenes
6a and 6b could be assembled in mode a e yields ia a one-po ,
wo-s ep p ocess om a ylenynes 5a and 5b bea ing an O and
a NTs g oup as linke s (Scheme 3, eq 1).
16
Double andem
p ocesses we e also accessible. Thus, a simple and s aigh o -
wa d en y o he linea benzodiCOT 9(benzo[1,2:4,5]di[8]-
annulene),
22
an appealing nonbenzenoid PAH s uc u e wi h
in iguing elec onic and a oma ic p ope ies,
23
was achie ed
om 1,4-die hynyl-2,5-di inylbenzene 7. The double Ru-
ca alyzed [2+2+2] cycloaddi ion o 7wi h alkyne 2a led o
he linea e ahyd o[3]phenylene 8in an excellen 80% yield.
The halogen- adical double ing opening o 8wi h NBS in
DCE occu ed une en ully o gi e he benzodiCOT 9in a
sa is ac o y 62% yield as a mix u e o U- and S-shaped
con o me s in solu ion, he S-shaped o m being 1.2 kcal mol−1
mo e s able han he U-shaped o m as shown by DFT
calcula ions (Scheme 3, eq 2).
24
1H NMR spec a o 9 e eal
he p esence o he wo con o me s a in a 1:2.5 a io, U- and
S-shaped, which could be he mally equilib a ed o 1:1.5 a io
a 100 °C. Single c ys als o 9sui able o X- ay diff ac ion
analysis we e g own om a solu ion in a ho CHCl3/hexane
mix u e by slow e apo a ion o he sol en s. 9shows an S-
shaped geome y wi h he b omine a oms on opposi e aces
wi h espec o he cen al benzene plane. In addi ion, he wo
eigh -membe ed ings a e conside ably ben up and down om
he plane o he cen al benzene uni wi h a la ge dihed al
angle o ∼138°. Simila o COT, he wo eigh -membe ed
ings adop a ub-shaped con o ma ion, wi h la ge bond leng h
al e na ion. The bonds o he cen al six-membe ed ings a e
wi hin he ypical ange o 1.39−1.40 Å, e ealing an a oma ic
benzenoid cha ac e . Scaling up was also easible as shown by
pe o ming a andem p ocess om ini ial enyne 1a and
a ylalkyne 2a wi hou he isola ion o dihyd obiphenylene 3a.
Thus, eac ion o 1a (8.1 mmol) and 2a (9.7 mmol) in MeOH
unde ca aly ic condi ions (as li le as 3% Ru) ollowed by a
apid eplacemen o he sol en wi h he apola DCE o
pe o m he adical eac ion allowed us o ob ain bCOT 4a
(2.1 g) in a 76% o e all yield (Scheme 3, eq 3).
In an effo o gain u he insigh s in o he eac ion
mechanism, DFT calcula ions we e pe o med o analyze all
possible adical pa hways.
24
We began he mechanis ic s udies
by elucida ing he selec i i y o he ini ial adical o ma ion
because wo diffe en adicals can be o med depending on he
abs ac ions o he e ia y hyd ogen H1o he cyclobu ene
moie y o one o he wo seconda y hyd ogens H2on he 1,3-
cyclohexadiene co e. E en hough e ia y C−H bonds a e
weake han seconda y ones, he p esence o he cyclobu ene
moie y d ama ically changes he eac i i y o he 1,3-cyclo-
hexadiene co e, making he o ma ion o he seconda y bis-
allylic adical I4.3 kcal mol−1mo e a o able han ha o he
allylic benzylic e ia y adical (Scheme 4). A omic spin
densi ies we e hen compu ed o he mo e s able allylic/
seconda y adical I, showing ha , as expec ed, i is mainly
di ided among he h ee ca bons o he cen al six-membe ed
ing.
24
We hen e alua e he h ee possible e olu ion pa hways o
he mos s able adical I(Figu e 1): (a) six-π-elec on
elec ocyclic ing opening ollowed by apping o he esul ing
adical wi h B 2 o affo d he obse ed cyclooc a e aene 4e
(ΔG⧧= 39.2 kcal mol−1, ed pa hway), (b) adical opening o
he cyclobu ane ing ollowed apping wi h B 2 o affo d
e phenyl II (ΔG⧧= 19.4 kcal mol−1, blue pa hway), and (c)
he mos a o able one (ΔG⧧= 5.7 kcal mol−1, black pa hway)
ha in ol es di ec b omina ion o he esonance s uc u e o I
wi h he adical in o he e ia y, allylic, and benzylic posi ion
o gi e ise o he b omina ed dihyd obiphenylene III. Once
III had been es ablished as he mos a o able p oduc o
adical b omina ion o 3e, he obse ed p oduc 4e would be
o med h ough a six-π-elec ocyclic ing opening.
24
The u ili y o he b omina ed bCOT’s4was es ed in he
p epa a ion o aluable COT-embedded PAH’s(Scheme 5).
Suzuki c oss-coupling be ween 4a and phenylbo onic acid
affo ds he expec ed phenyl-subs i u ed bCOT 10 in 70% yield
(Scheme 5, eq 1). Sonogashi a couplings we e also
sa is ac o ily ca ied ou unde ypical eac ion condi ions.
Alkynyl-subs i u ed COT’s11a and 11b we e ob ained in good
o excellen yields using ime hylsilylace ylene 2l and
Scheme 3. He e oannula ed bCOT’s 6a and 6b, Linea
BenzodiCOT 9, and Scale-Up Syn hesis o bCOT 4a
a
a
The ORTEP d awing o 9shows ellipsoids a he 50% con ou
p obabili y le el.
Scheme 4. Bond Dissocia ion Ene gies (BDE’s) o H1and
H2
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alkynylaniline 2m, espec i ely (Scheme 5, eq 2). To ou
deligh , an efficien Sonogashi a coupling be ween 4a and
alkynylCOT 11a′( om desilyla ion o 11a) ende s
une en ully he in e es ing bis-COT de i a i e 11c,as
confi med by X- ay analysis (Scheme 5, eq 3).
25
Finally,
ea men o 4a wi h KO Bu
10
gene a es a s ained cyclic
alkyne ha could be subsequen ly apped as a dienophile wi h
e aphenylcyclopen adienone in a Diels−Alde eac ion
affo ding he π-ex ended dibenzoCOT 12 in e y good yield
(Scheme 5, eq 4). No e he highe eac i i y o he iple bond
in plana ized sys ems con aining one benzo- used eigh -
membe ed ing ( , 25 °C) as compa ed o he ypical
dibenzo- used de i a i e (Ph2O eflux, >250 °C).
26
In conclusion, we ha e de eloped a gene al syn he ic
me hod o cons uc ing a new class o polycyclic a enes
embedded wi h a b omina ed (halogena ed) COT ing ia a
andem Ru-ca alyzed [2+2+2] cycloaddi ion o a ylenynes o
dihyd obiphenylenes ollowed by halogen- adical ing opening.
The p ocess in ol es he ini ial o ma ion o a bis-allylic adical
a he 1,3-cyclohexadiene co e o he dihyd obiphenylene.
Then, halogena ion a he b idgehead posi ion o he
benzocyclobu ene ing ollowed by a subsequen elec ocyclic
ing opening ende s he obse ed cyclooc a e aene. This
p o ocol p o ides a new syn he ic app oach o polycyclic
a enes used wi h an eigh -membe ed ing (bCOT), which is
expec ed o be applicable o he syn hesis o di e se cu ed
nanoca bons.
■ASSOCIATED CONTENT
*
sıSuppo ing In o ma ion
The Suppo ing In o ma ion is a ailable ee o cha ge a
h ps://pubs.acs.o g/doi/10.1021/acs.o gle .1c01881.
Gene al expe imen al p ocedu es, X- ay c ys allog aphic
da a, NMR spec a, and DFT calcula ions (PDF)
Compu a ional de ails, ee ene gy p ofile o he
isome iza ion o benzodiCOT 9 om he U- o S-
shaped con o me s, comple e ee ene gy p ofile o he
adical b omina ion o dihyd obiphenylene 3e and six-π-
elec on elec ocyclic ing opening o b omina ed
dihyd obiphenylene III, na u al bond o bi al analysis,
e e ences, and Ca esian coo dina es, ene gy alues, and
imagina y equencies o all o he s a iona y poin s
in ol ed h oughou he DFT s udy (PDF)
Accession Codes
CCDC 2085992−2085994 con ain he supplemen a y c ys-
allog aphic da a o his pape . These da a can be ob ained
ee o cha ge ia www.ccdc.cam.ac.uk/da a_ eques /ci ,o by
emailing [email p o ec ed], o by con ac ing The
Camb idge C ys allog aphic Da a Cen e, 12 Union Road,
Camb idge CB2 1EZ, UK; ax: +44 1223 336033.
■AUTHOR INFORMATION
Co esponding Au ho
Ca los Saá −Cen o Singula de In es igaciónenQuímica
Biolóxica e Ma e iais Molecula es (CiQUS), Depa amen o
de Química O gánica, Uni e sidade de San iago de
Compos ela, 15782 San iago de Compos ela, Spain;
o cid.o g/0000-0003-3213-4604; Email: ca los.saa@
usc.es
Au ho s
Jesus Bello-Ga cía −Cen o Singula de In es igaciónen
Química Biolóxica e Ma e iais Molecula es (CiQUS),
Depa amen o de Química O gánica, Uni e sidade de
San iago de Compos ela, 15782 San iago de Compos ela,
Spain
Damián Padín −Cen o Singula de In es igaciónenQuímica
Biolóxica e Ma e iais Molecula es (CiQUS), Depa amen o
Figu e 1. F ee ene gy p ofiles o he adical b omina ion o 3e.
Ene gies a e ela i e o 3e and a e mass balanced.
Scheme 5. Syn he ic Applica ions o B omina ed bCOT’s
a
a
The ORTEP d awing o 11c shows ellipsoids a he 50% con ou
p obabili y le el.
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h ps://doi.o g/10.1021/acs.o gle .1c01881
O g. Le . 2021, 23, 5539−5544
5542
de Química O gánica, Uni e sidade de San iago de
Compos ela, 15782 San iago de Compos ela, Spain;
o cid.o g/0000-0002-3841-727X
Jesus A. Va ela −Cen o Singula de In es igaciónenQuímica
Biolóxica e Ma e iais Molecula es (CiQUS), Depa amen o
de Química O gánica, Uni e sidade de San iago de
Compos ela, 15782 San iago de Compos ela, Spain;
o cid.o g/0000-0001-8499-4257
Comple e con ac in o ma ion is a ailable a :
h ps://pubs.acs.o g/10.1021/acs.o gle .1c01881
No es
The au ho s decla e no compe ing financial in e es .
■ACKNOWLEDGMENTS
This wo k has ecei ed financial suppo om MINECO
(P ojec CTQ2017-87939R and ORFEO-CINQA Ne wo k
RED2018-102387-T), he Xun a de Galicia (P ojec ED431C
2018/04 and Cen o singula de in es igación de Galicia
acc edi a ion 2019-2022, ED431G 2019/03), and he Eu o-
pean Union (Eu opean Regional De elopmen Fund). J.B.-G.
hanks Xun a de Galicia o a p edoc o al con ac . The
au ho s a e also g a e ul o he CESGA (Xun a de Galicia) o
compu a ional ime. Dedica ed o P o . K. Pe e C. Vollha d ,
Depa men o Chemis y, Uni e si y o Cali o nia, Be keley,
USA, on he occasion o his 75 h bi hday.
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